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International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491
Vol 5, Suppl 4, 2013
Research Article
FORMULATION, EVALUATION AND COMPARISION OF DISSOLUTION PROFILES OF
ESLICARBAZEPINE ACETATE IMMEDIATE RELEASE TABLETS USING NATURAL BINDERS
AGAINST SYNTHETIC BINDER
SWETA AGARWAL*, P. V. KAMALA KUMARI, Y. SRINIVASA RAO
Department of Pharmaceutics, Vignan Institute of Pharmaceutical technology, Duvvada, Visakhapatnam. Email: [email protected]
Received: 08 Aug 2013, Revised and Accepted: 29 Sep 2013
ABSTRACT
Objective: The objective of the present study was to formulate, evaluate and compare the dissolution profiles of Eslicarbazepine acetate (ESL)
immediate release tablets using natural binders like tapioca starch, maize starch and galbanum, against the synthetic binder like Polyvinyl
Pyrrolidone (PVP).
Methods: These natural binders were used as novel excipients which formed weak attractive bonds with the drug by complexation during wet
granulation and increased the solubility of ESL. Each of these natural and synthetic binders was used separately in different concentrations to
prepare immediate release tablets of ESL. Dissolution profiles of these tablets were compared.
Results: The in-vitro drug release of F4 (with galbanum 1%) was highest 98.78%, whereas the least drug release of 61.66% was shown by F12 (with
PVP 3%).
Conclusion: It was seen that the tablets with natural binders showed better release characteristics in comparison to the tablets with synthetic
binder PVP. Formulation with galbanum 1% showed best release profile. Galbanum also has antiepileptic property which can act synergistically
with Eslicarbazepine acetate to treat seizures. It was also seen that among the various concentrations of binders used formulations with 1% binder
showed better release characteristics when compared to 2% and 3%.
Keywords: Binders, Solubility, Novel, Dissolution, concentration
INTRODUCTION
Immediate release tablets are designed to disintegrate and release
their medicaments with no special rate controlling features such as
special coatings and other techniques. Immediate release dosage
forms are most commonly formulated when the half life of the drug
is more and there is no necessity of frequent dosing. This also serves
as an advantage for patient compliance. Other reason for
formulating immediate release dosage form is rapid response. [1]
In the present study, the API, Eslicarbazepine acetate is a pro-drug,
which is metabolized to active form S-licarbazepine which is a
potent form of the drug without any toxication, whereas
oxcarbazepine forms both R and S form, the R form produces toxic
metabolites. ESL has a half life of 13-20hrs, which means it is a
suitable candidate for immediate release dosage form. It has almost
complete bioavailability. [2, 3]
Novel excipients are used which enhance the solubility of poorly
soluble drug Eslicarbazepine acetate by forming complexes with
them. The mechanism by which it improves solubility is more
closely related to complexation involving a weak interaction
between the novel excipient and the poorly soluble drugs. It is a
solubilization process, whereby addition of a large amount of second
water soluble solute, results in an increase in the aqueous solubility
of first solute. The starches used, also have a good disintegrating
property. When the mucilage is prepared, starch converts into
glucose and dextrin. [4, 5]
The Natural Binders were used in three different concentrations 1%,
2%, 3% to formulate immediate release tablets of Eslicarbazepine
acetate using wet granulation technique. The synthetic binder PVP
was also used in three different concentrations 1%, 2%, 3%. 12
different formulations of immediate release dosage form were
prepared.
MATERIALS AND METHODS
Materials
Eslicarbazepine acetate was obtained as a gift sample from Ami life
sciences Pvt. Ltd. CrossCarmellose sodium; PVP K 30 was obtained
from Yarrow Chem. Products, Mumbai, Tapioca starch and maize
starch was obtained from Surya min chem., Magnesium stearate,
Talc was obtained from Molychem. Galbanum was obtained from a
local vendor.
Table 1: It shows formula for the preparation of immediate release tablets of Eslicarbazepine acetate
Formulation
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
Eslicarbazepine acetate
200mg
200mg
200mg
200mg
200mg
200mg
200mg
200mg
200mg
200mg
200mg
200mg
CCS (mg)
10
10
10
10
10
10
10
10
10
10
10
10
Tapioca starch
1%
2%
3%
-
Maize starch
1%
2%
3%
-
Galba-num
1%
2%
3%
-
PVP
1%
2%
3%
Magnesium Stearate
4mg
4mg
4mg
4mg
4mg
4mg
4mg
4mg
4mg
4mg
4mg
4mg
Talc
6mg
6mg
6mg
6mg
6mg
6mg
6mg
6mg
6mg
6mg
6mg
6mg
Agarwal et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 4, 192-194
granules were passed through sieve of mesh number 22. The dried
granules that passed through the 20 mesh sieve were lubricated
with magnesium stearate and talc. This mixture was subjected to
different pre formulation studies namely Bulk density, Tapped
Density and Angle of Repose, compressibility index and Hausner’s
ratio. Finally the dried granules were compressed as tablets by MiniPress compression machine.
Method of Preparation
Twelve different formulations of Eslicarbazepine acetate immediate
release tablets are prepared using ingredients as given in Table no.1.
Different concentrations of natural binders were used to prepare
immediate release tablets of Eslicarbazepine by wet granulation
method. Crosscarmellose sodium was used as a super disintegrant,
Tapioca Starch, maize starch and galbanum were used as natural
binders and PVP is used as a synthetic binder. Magnesium stearate
was used as a lubricant and talc was used as a glidant.
RESULTS AND DISCUSSION
Pre-Compression characterization of API and granules:
Twelve different formulations of Eslicarbazepine acetate were
prepared. The pure drug Eslicarbazepine acetate was mixed with
Crosscarmellose sodium and the mixture was wet granulated using a
natural or synthetic binder of different concentrations 1%, 2%, 3%.
The granules were passed through sieve of mesh number 10. Then
these granules were dried in a hot air oven at 60°C. The dried
The compatibility of drug and each excipient was studied using FTIR. It was found that there was no interaction between any excipient
and the drug. The lubricated powder blend was evaluated for
density parameters like bulk density, tapped density,
compressibility index and Hausner’s ratio was calculated to estimate
the flow properties.
[
Table 2: It shows pre-compression characterization of API and dried granules
Formulation Code
API
F1
F2
F3
F4
F6
F7
F8
F9
F10
F11
F12
Bulk density (g/ml)
0.528
0.512
0.520
0.488
0.50
0.492
0.484
0.492
0.496
0.48
0.476
0.48
Tapped density (g/ml)
0.628
0.600
0.610
0.610
0.590
0.600
0.576
0.600
0.590
0.57
0.58
0.585
Angle of Repose (°)
28.8
27.6
28.98
29.68
29.03
29.07
27.42
29.55
27.44
28.05
27.9
29.16
Carr’s Index (%)
15.9
14.6
14.7
20
15.2
18
15.9
18
15.9
15.9
17.9
17.9
Hausner Ratio
1.18
1.17
1.17
1.25
1.18
1.21
1.19
1.21
1.18
1.18
1.21
1.21
F9-91.41%, F10-68.91%, F11-64.47%, F12-61.66%. Among all the
formulations F7 shows the best release profile when compared to
other eleven formulations. Also it was observed that the release
profile of tablets with natural binders have better release
characteristics when compared to tablets with synthetic binder.
Among the natural excipients used, galbanum showed the properties
of a novel excipient which when used in the formulation of tablet
showed better drug release. Galbanum also has antiepileptic effect
which can act synergistically with Eslicarbazepine acetate without
producing any toxicity. Among the different concentrations of
binders used 1% binder in all the formulations showed better
release characteristic when compared to 2% and 3%. The results are
given graphically in figure 1.
Post Compression characterization of tablets
Post compression characterization of tablets was carried out by
testing their hardness, friability, uniformity of weight, thickness,
wetting time, disintegration time and drug content.
The in-vitro dissolution studies were performed for the twelve
formulations to evaluate the dissolution characteristic of
Eslicarbazepine acetate tablets in the presence of Binders used as
novel excipients. Also the dissolution profiles of all the formulations
were compared and the optimized formulation among them was
selected. The results are presented in Table No.4. The dissolution
study of all the formulation was found to be F1-95.04%, F2-92.23%,
F3-90.81%, F4-88.69%, F5-84.08%, F6-81.3%, F7-98.78%, F8-94.22,
Table 3: It shows post-compression characterization of tablets
Parameter
Hardness (kg/cm2)
Friability (%w/w)
Thickness (mm)
Diameter (mm)
Wetting time (Sec)
Weight Variation (mg)
In-Vitro Disintegration time (sec)
Drug Content (%)
Formulation
F1
F2
4.9
4.3
0.3
0.22
2.9
2.92
4.9
4.88
30
28
222.1
221
20.5
22
97.04
96.32
F3
4.5
0.37
2.96
4.96
31
220
22.5
95.89
F4
4.5
0.15
2.89
4.98
34
221.3
23.5
97.7
F5
4.6
0.22
2.92
4.89
36
219
24
98.1
F6
4.8
0.30
2.88
4.93
37
220
25
97
F7
4.2
0.22
2.96
4.91
26
220.5
18
99
F8
4.3
0.30
2.90
4.97
28
221
20
97.2
F9
4.5
0.30
2.86
4.94
29
219
21
96.3
F10
4.1
0.37
2.9
4.95
37
221.3
27
92
F11
4.3
0.30
2.91
4.88
39
222
28
92.1
F12
4.5
0.37
2.9
4.9
40
223
30
93
Table 4: It shows in-vitro drug release of various formulations
Formulation
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
5
26.6
25.5
22.93
26.04
25.09
20.86
31.77
30.6
28.69
14.18
12.68
10.63
10
44.78
41.7
36.98
41.61
37.8
35.34
48.1
43.85
40.66
27.81
25.96
23.80
15
53.23
51.65
48.38
50.48
47.56
44.31
57.3
53.15
49.06
33.76
31.41
28.71
20
65.37
61.77
58.68
58.47
55.66
52.39
70.60
66.49
61.69
41.75
38.61
91.41
30
77.37
75.73
70.60
72.43
71.56
69.21
80.31
75.10
72.70
53.23
50.80
68.91
45
90.68
88.52
87.58
85.96
80.78
80.01
93.5
90.73
88.41
62.48
60.87
64.47
60
95.04
92.23
90.81
88.69
84.08
81.3
98.78
94.22
91.41
68.91
64.47
61.66
193
Agarwal et al.
Int J Pharm Pharm Sci, Vol 5, Suppl 4, 192-194
Cummulative percentage drug released
(%)
120
F1
100
F2
F3
80
F4
F5
60
F6
F7
40
F8
F9
20
F10
F11
0
F12
0
5
10
15
20
30
45
60
Time (Min)
Fig. 1: It shows comparison of dissolution profiles of different formulations
The compressed tablets were characterized by their physical
properties. The average tablet weight was determined for 20 tablets.
Tablet hardness was tested using Monsanto tablet hardness tester.
Friability of the tablets was determined by Roche friabilator. Tablet
friability was calculated as the percentages of weight loss of 20
tablets after 100 rotations. The physical parameters of granules
were provided in Table No. 2.
Principal Y.Srinivasa Rao for providing full assistance of materials
and equipments during my research work.
CONCLUSION
2.
Immediate release tablets of Eslicarbazepine acetate was prepared by
wet granulation method using various natural binders and a synthetic
binder PVP. It was seen that the formulations with natural binders
showed better release characteristics when compared to the
formulations with synthetic binder PVP. Among the natural binders,
galbanum showed the best dissolution profile and can be used
successfully in future to prepare antiepileptic tablets because it has an
optimum binding effect and also antiepileptic property. Among the
various concentrations of binders used formulations with 1% binder
showed better release characteristics when compared to 2% and 3%.
ACKNOWLEDGEMENTS
I record my gratification to my guide Dr.P.VKamala Kumari for her
supervision, guide and advice. I also record my gratification to my
REFERENCES
1.
3.
4.
5.
Lachman L, Lieberman HA, Kanig JL. The Theory and practice of
Industrial pharmacy. Varghese publishing House, Mumbai;
2009, p. 317
Kalia, Anupama, Shelly Khurana, and Neena Bedi. "Formulation
and evaluation of mouth dissolving tablets of oxcarbazepine.
International Journal of Pharmacy and Pharmaceutical
sciences. 1.1 (2009): 12-23.
Singh, Rajinder P., and Jorge J. Asconapé. A Review of
eslicarbazepine Acetate for the Adjunctive Treatment of
partial-Onset epilepsy. Journal of central nervous system
disease 3 (2011): 179.
Savjani, Ketan T., Anuradha K. Gajjar, and Jignasa K. Savjani.
"Drug solubility: Importance and enhancement techniques”.
ISRN pharmaceutics volume 2012; 2012.
Wagh, Milind P., et al. "Formulation and evaluation of fast
dispersible tablets of aceclofenac, using different
superdisintegrant. International Journal of Pharmacy and
Pharmaceutical Sciences 2.1 (2010): 154-157
194